Melanoma
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Jun 01 – Jun 08, 2026
Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase 2b KEYNOTE-942 Study.
J CLIN ONCOL · Q1 JOURNAL - RANK #6/326TOP-TIER
This randomized phase 2b KEYNOTE-942 study evaluated intismeran (mRNA neoantigen therapy) plus pembrolizumab versus pembrolizumab alone in 157 patients with resected stage IIIB-IV melanoma. Over 60.3 months median follow-up, the combination prolonged recurrence-free survival (HR 0.510; 95% CI 0.294-0.887) and distant metastasis-free survival (HR 0.411; 95% CI 0.200-0.843) with a favorable overall survival trend (HR 0.471; 95% CI 0.165-1.345). Safety was manageable with no new signals. The combination showed increased T-cell receptor clonality and greater novel clone expansion in recurrence-free patients.
10.1200/JCO-26-00835
May 25 – Jun 01, 2026
Accuracy of Index Lymph Node Pathology in Predicting Overall Response to Neoadjuvant Immunotherapy for Clinical Stage III Melanoma: Results From the Prospective NeoACTIVATE Arm C (NCT03554083) Substudy.
ANN SURG ONCOL · Q1 JOURNAL - RANK #39/312
This preplanned prospective substudy of the multicenter NeoACTIVATE Arm C trial evaluated whether pathology of a clipped index lymph node (ILN) predicts whole-nodal-basin response after neoadjuvant atezolizumab plus tiragolumab in resectable clinical stage III melanoma, using International Neoadjuvant Melanoma Consortium criteria and therapeutic lymph node dissection. Among 34 enrolled patients, 30 underwent TLND per protocol; 2/30 (6.7%) showed discordance (ILN pathologic complete response [pCR] but residual disease in non-ILNs), yielding an ILN pCR false-negative rate of 13.3%. In the subgroup with a single involved node at baseline (n=8), pathologic major response was 75% and concordance was 100%. The study concludes ILN pathology alone may not fully reflect basin status, advising caution in de-escalation based solely on ILN response and calling for trials of limited nodal resection.
10.1245/s10434-026-19899-1
Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin: a phase I study in patients with advanced and/or metastatic solid tumors.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of cergutuzumab amunaleukin (CA) in 60 patients with advanced/metastatic CEA-positive solid tumors. The study comprised two parts: single-dose (0.1-6 mg, n=5) and multiple ascending doses (10-40 mg q2w, n=31; 6-30 mg qw, n=24), establishing an MTD of 30 mg q2w with dose-limiting toxicities including Gr4 hypophosphatemia and thrombocytopenia. Pharmacokinetics showed dose-proportional exposure (6-40 mg), and pharmacodynamics revealed preferential expansion of CD8+ T and NK cells. No objective responses were observed, but 11% (6/53) achieved stable disease (median duration 4.5 months), supporting further combination therapy development.
10.1016/j.esmoop.2026.107697
May 18 – May 25, 2026
Phase 1/2 study of pegenzileukin, a pegylated recombinant non-alpha IL-2, with cemiplimab for the treatment of advanced unresectable or metastatic skin cancers.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This phase 1/2 open-label, multicenter clinical trial evaluated pegenzileukin, a pegylated non-alpha IL-2, in combination with cemiplimab for advanced melanoma (MM) and cutaneous squamous cell carcinoma (CSCC). The primary endpoint was objective response rate (ORR), which reached 40% in MM and 56.3% in CSCC at the recommended phase 2 dose (RP2D), with a duration of response ≥12 months in 75.0% and 85.7% of responders, respectively. Secondary endpoints included progression-free survival (PFS), with rates of 55.0% in MM and 70.7% in CSCC at 6 months. The treatment showed manageable safety, with common adverse events being mild infusion-related reactions and robust NK and CD8 T-cell expansion supporting its mechanism of action (NCT04913220).
10.1136/jitc-2025-014347
Use of circulating tumour DNA to prospectively guide a switch from targeted to immune therapy in BRAF mutant advanced melanoma: the randomised phase II CAcTUS trial.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
The randomized, parallel-arm phase II CAcTUS trial prospectively evaluated circulating tumour DNA (ctDNA) to guide transition between targeted therapy (TT) and checkpoint inhibitor immunotherapy (CPI) for BRAF mutant advanced melanoma. Twenty-one patients were randomized to receive TT or CPI, switching treatments based on either progression or achieving ≥80% reduction of BRAF variant allele frequency (VAF) in ctDNA, with 100% critical results obtained within 7 days (95% CI: 94-100%) and 100% TT patients achieving ≥80% reduction (95% CI: 80-100%). Secondary outcomes assessed progression-free and overall survival, with no new safety signals observed. The findings demonstrate ctDNA’s feasibility for timely treatment decisions, optimizing therapy sequencing.
10.1038/s41467-026-72735-8
Five-Year Survival with Tebentafusp in Metastatic Uveal Melanoma.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
An international, open-label, randomized phase 3 trial (NCT03070392) evaluated 5-year overall survival with tebentafusp versus investigator’s choice (pembrolizumab, ipilimumab, or dacarbazine) in previously untreated HLA-A*02:01-positive adults with metastatic uveal melanoma, stratified by LDH; exploratory endpoints included ctDNA dynamics. After ≥5 years’ follow-up, median OS was 21.6 months with tebentafusp versus 16.9 months with control (stratified HR 0.67; 95% CI 0.54–0.85), and 5-year OS rates were 16% versus 8%. Benefit extended to poor-prognosis subgroups (e.g., tumors ≥10 cm or RECIST progressive disease), and post hoc analyses suggested longer OS with treatment beyond radiographic progression. Undetectable baseline ctDNA or ≥50% ctDNA reduction by week 9 correlated with longer OS, supporting durable survival benefit of tebentafusp.
10.1016/j.annonc.2026.05.695
Lipid Nanoparticle-encapsulated mRNA-2752 Encoding Human OX40L, IL-23, and IL-36γ Plus Durvalumab Induces an Immunostimulatory Effect Within the Tumor Microenvironment in Patients with Advanced Solid Tumors.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This phase 1 study (NCT03739931) evaluated intratumoral mRNA-2752 (encoding OX40L, IL-36γ, and IL-23) as monotherapy (Arm A) or combined with durvalumab (Arm B) in advanced solid tumors, with primary objectives of safety, tolerability, maximum tolerated dose (MTD), and objective response rate (ORR) per RECIST v1.1 in CPI-resistant melanoma. Among 134 patients (Arm A n=19; Arm B n=115), the MTD was not reached and a recommended dose for expansion ≤8 mg was selected; dose-limiting toxicities were two grade 2 cytokine-release syndrome events in Arm B. Treatment-related adverse events were mostly grade 1/2; grade 3 mRNA-2752–related events occurred in 1/19 (5.3%) in Arm A and 29/115 (25.2%) in Arm B, and confirmed ORR in CPI-resistant melanoma (n=28) was 17.9% (95% CI 6.1–36.9%) with disease control rate 42.9% (95% CI 24.5–62.8%). Biomarkers showed increased peripheral cytokines and sustained inflammatory tumor microenvironment responses, supporting antitumor activity and further development.
10.1158/1078-0432.CCR-25-4643
Phenotypic and Functional Characteristics of CD8+ T cells Predict Clinical Outcome Following TIL Therapy in a Randomized Phase III Trial in Advanced Melanoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This study evaluated the efficacy of tumor-infiltrating lymphocytes (TIL) therapy in a randomized Phase III clinical trial (TIL-NKI/CCIT) for advanced melanoma. The trial compared TIL treatment to ipilimumab in 80 patients with unresectable stage IIIC and IV cutaneous melanoma, focusing on biomarkers of therapeutic response. Key findings showed a strong correlation between the number of infused CD8+TCRαβ+ T cells and progression-free survival (PFS); higher frequencies of these cells were associated with improved PFS at six months (p<0.0001). The authors concluded that CD8+ T cell characteristics, including phenotype, tumor reactivity, and persistence, are critical predictors of clinical outcomes following TIL therapy.
10.1158/1078-0432.CCR-25-4097
May 11 – May 18, 2026
Phase I trial of CJRB-101 plus pembrolizumab in patients with metastatic non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This first-in-human, two-part, phase I trial evaluated CJRB-101 (1×10 or 4×10 CFU/day) plus pembrolizumab (200 mg Q3W) in 42 patients with advanced NSCLC, melanoma, or HNSCC in ICI-naïve and ICI-refractory settings. In preclinical PDX models, CJRB-101 plus pembrolizumab showed enhanced tumor growth inhibition (TGI) of 61.9% versus 77.3% with CJRB-101 alone, alongside M2-to-M1 repolarization and cytotoxic T-cell activation. None of the patients experienced dose-limiting toxicities, and in ICI-naïve NSCLC with PD-L1 >50% (n=12), the overall response rate reached 58%, disease control was 75%, and the median progression-free survival was 9 months. The combination was well-tolerated, including in ICI-refractory cases with ORR of 5% and DCR of 41%, supporting further investigation of CJRB-101 plus pembrolizumab in advanced solid tumors.
10.1136/jitc-2025-014702
A phase II peri-operative study of pembrolizumab plus lenvatinib for mucosal melanoma.
NAT COMMUN · Q1 JOURNAL - RANK #10/135TOP-TIER
This single-arm phase II study evaluated neoadjuvant pembrolizumab plus lenvatinib followed by surgery and adjuvant pembrolizumab in 21 patients with resectable mucosal melanoma (NCT04622566), including exploratory biomarker analysis. The primary endpoint was pathological complete response (pCR) rate (9.5%), with secondary outcomes including major pathologic response (MPR, 19.0%), pathologic response rate (38.1%), median relapse-free survival (14.8 months; 1-year rate: 61.9%), and overall survival (not reached). No grade 4-5 toxicities occurred, and biomarker analysis revealed immune-inflamed microenvironments in responders with activated CD4⁺/CD8⁺ T cell signatures. The study concluded that immune features like TCR persistence and T cell spatial proximity may guide peri-operative therapy optimization despite not meeting the primary endpoint.
10.1038/s41467-026-73190-1
May 04 – May 11, 2026
Beyond empiric checkpoint escalation: Insights from KEYVIBE-010.
MED-CAMBRIDGE · Q1 JOURNAL - RANK #11/195TOP-TIER
KEYVIBE-010 is a Phase 3 prospective human clinical trial comparing adjuvant vibostolimab combined with pembrolizumab to pembrolizumab monotherapy in patients with resected, high-risk melanoma. The study concluded early due to futility, as the combination therapy had higher toxicity without improved efficacy over the monotherapy control group. The trial provides evidence against the utility of combined checkpoint inhibition in this clinical setting. Results highlight the challenges in extending checkpoint inhibitor combinations to the adjuvant treatment of high-risk melanoma.
10.1016/j.medj.2026.101105
The Phase Ib IMPACT Trial of Intramuscular Personalized Neoantigen Synthetic Long Peptide Vaccines in Patients with Advanced Melanoma and Renal Cell Carcinoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
The Phase Ib IMPACT Trial evaluated the safety and immunogenicity of intramuscular personalized neoantigen synthetic long peptide (SLP) vaccines in 12 patients with advanced melanoma (n=9) or renal cell carcinoma (n=3). Patients received vaccines containing ~20 predicted neoantigen peptides with poly-ICLC, monitored for adverse events and immune responses. The vaccine was well-tolerated, with 53% of peptides per patient inducing immunogenic responses, including CD8⁺ and CD4⁺ T-cell activation, and enhanced CD8⁺ infiltration in tumor biopsies. The study concludes that intramuscular neoantigen SLP vaccination is safe and induces robust mutation-specific T-cell immunity, supporting its potential as a peptide-based cancer vaccine strategy.
10.1158/1078-0432.CCR-25-4271
Real-world study of SHR-1210 plus apatinib in the treatment of BRAF-negative mucosal melanoma: efficacy, safety and implications of precision medicine.
FRONT IMMUNOL · Q1 JOURNAL - RANK #32/183
This single-arm, phase II nonrandomized clinical trial aimed to evaluate the efficacy and safety of SHR-1210 in combination with Apatinib as a late-line treatment for advanced mucosal melanoma. Thirteen patients received intravenous SHR-1210 (200 mg every three weeks) and oral Apatinib (250 mg daily). The disease control rate (DCR) reached 100%, with a median progression-free survival (PFS) of 5.17 months (95% CI 3.27-10.27) and median overall survival (OS) of 29.9 months (95% CI 15.26-44.54). The study concluded that the combination therapy shows promising disease control potential but emphasizes the need for increased sample size for further validation.
10.3389/fimmu.2026.1755669
Apr 27 – May 04, 2026
Phase I trial of a heat-conditioned tumor lysate vaccine (TRIMELVax) in anti-PD-1 refractory melanoma: safety and immunological aspects (NCT06556004).
BRIT J CANCER · Q1 JOURNAL - RANK #47/326
This Phase I study evaluated TRIMELVax, a heat-conditioned tumor lysate vaccine, in 17 advanced melanoma patients who were refractory to anti-PD-1 therapy. Investigators administered four subcutaneous doses every four weeks to assess safety, immunogenicity, and preliminary efficacy. One patient exhibited a partial response and six had stable disease (41% disease control), with a median overall survival of 14 months and median progression-free survival of 5.2 months. Vaccine-induced immune activation was evidenced by increases in CXCR3 on CD8⁺ T cells and reduced CD39 expression, supporting further investigation in larger trials.
10.1038/s41416-026-03459-1
First-in-human use of recombinant IL-7 to potentiate antigen-specific T cell therapy: a single patient case study.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This first-in-human study evaluated recombinant IL-7 combined with adoptively transferred antigen-specific memory CD8 T cells in a single patient with refractory metastatic uveal melanoma, without lymphodepletion. Serial peripheral blood sampling with single-cell immune repertoire profiling demonstrated in vivo proliferation and expansion of a stem cell memory population, achieving >79% predominance of total circulating T cells by 3 weeks post-infusion. The patient’s disease ultimately progressed, but the findings established safety and proof of concept for IL-7 in enhancing T cell expansion and memory differentiation. This prospective single-arm clinical trial involved active treatment assignment (IL-7 plus T cells) and reported human results directly relevant to cancer therapy.
10.1136/jitc-2026-014822
Safety and efficacy of intratumoural anti-CTLA4 with intravenous anti-PD1.
NATURE · Q1 JOURNAL - RANK #2/135TOP-TIER
This study aimed to evaluate the safety and efficacy of intratumoural ipilimumab (anti-CTLA4) combined with intravenous nivolumab (anti-PD1) in a randomized multicentre phase 1b trial of 61 patients with untreated metastatic melanoma. Patients were assigned 2:1 to receive intravenous nivolumab (1 mg/kg) plus either intratumoural ipilimumab (0.3 mg/kg) or intravenous ipilimumab (3 mg/kg), with the primary end-point being the incidence of grade 3/4 adverse events at six months. The intratumoural arm showed significantly lower grade 3/4 toxicity (22.6% vs 57.1%), while maintaining high objective response rates in injected (65.7%) and uninjected (50%) lesions. These results indicate that local administration of anti-CTLA4 can reduce systemic toxicity and preserve antitumour efficacy, highlighting the importance of an intratumoural immune environment for clinical benefit.
10.1038/s41586-026-10341-w
Apr 20 – Apr 27, 2026
IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in melanoma.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
This Phase 3, open-label trial investigated the combination of IO102-IO103 immune-modulatory cancer vaccine with pembrolizumab compared to pembrolizumab alone in 407 patients with untreated advanced melanoma randomized 1:1. The primary endpoint, progression-free survival (PFS) by blinded independent central review, showed a median of 19.4 months for the combination versus 11.0 months for pembrolizumab alone, but statistical significance (P = 0.0558 vs. P ≤ 0.045) was missed. Subgroup analyses revealed a notable PFS benefit, especially in PD-L1-negative patients (16.6 vs. 3.0 months; HR = 0.54). Treatment was well-tolerated, with no increase in severe systemic adverse events in the vaccine arm. The study highlighted the combination’s potential, despite not achieving statistical significance for the primary endpoint.
10.1016/j.annonc.2026.04.010
MONETTE: A Randomized Phase II Study of Ceralasertib plus Durvalumab or Ceralasertib Monotherapy in Patients with Advanced Melanoma Resistant to PD-(L)1 Inhibition.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This randomized, open-label phase II trial evaluated whether adding durvalumab to ceralasertib improves outcomes in 108 patients with unresectable or metastatic melanoma progressing on prior PD-(L)1 ± CTLA-4 therapy. Participants were randomized 2:1 to ceralasertib 240 mg twice daily on days 1-7 plus durvalumab 1500 mg intravenously on day 8 of each 28-day cycle, or to the same schedule of ceralasertib monotherapy. Objective response rates were 9.3 % (95 % CI 4.3-16.9) for the combination versus 5.8 % (95 % CI 1.2-15.9) for monotherapy; median progression-free survival was 2.0 vs 1.9 months (HR 0.80), and median overall survival was 16.0 vs 12.3 months (HR 0.81). Both regimens were well-tolerated, and exploratory biomarker analyses suggested higher baseline intratumoral CD8+ T-cell counts may correlate with longer survival.
10.1158/1078-0432.CCR-25-3951
Cellular neighborhoods govern antitumor T-cell infiltration following anti-CTLA-4 in melanoma with primary resistance to anti-PD-1.
CANCER DISCOV · Q1 JOURNAL - RANK #10/326TOP-TIER
This phase 2 trial (SWOG S1616, NCT03033576) prospectively evaluated the combination of ipilimumab with continued nivolumab versus ipilimumab alone in patients with advanced melanoma resistant to anti-PD-1/L1 therapies. The study analyzed baseline and on-therapy biopsies using transcriptomics and spatial proteomics to characterize tumor microenvironment changes. Key findings included improved outcomes with combination therapy and identification of specific cellular neighborhoods (e.g., networks of activated CD8 T cells near melanoma cells) associated with response, while progressing biopsies showed impaired T-cell infiltration adjacent to plasma cells. The results define transcriptomic and spatial cellular architectures associated with reversing anti-PD-1 resistance through added anti-CTLA-4 therapy.
10.1158/2159-8290.CD-25-1745
Intratumoral sotigalimab with pembrolizumab induces rapid activation of antigen presenting cells and drives anti-tumor responses in non-injected tumors in metastatic melanoma: A phase I/II study.
CANCER DISCOV · Q1 JOURNAL - RANK #10/326TOP-TIER
This multicenter phase I/II clinical trial assessed intratumoral sotigalimab (anti-CD40 agonist) plus pembrolizumab in 32 immune checkpoint blocker-naïve metastatic melanoma patients. Safety and objective response rate (ORR) were primary endpoints, with findings showing sotigalimab was well tolerated; at the recommended Phase 2 dose, ORR reached 50% and disease control rate (DCR) was 92%. ORR was 67% in injected and 50% in non-injected tumors, with multiomic analyses demonstrating increased immune cell infiltration and activation, and higher T-cell clonality across tumors. The study concludes that sotigalimab plus pembrolizumab drives robust anti-tumor immunity in both injected and distant tumors, correlating immunologic changes with clinical response.
10.1158/2159-8290.CD-25-1551
Apr 06 – Apr 13, 2026
Efficacy and safety of regorafenib in patients with advanced pretreated melanoma: results of the RegoMel phase II clinical trial.
ESMO OPEN · Q1 JOURNAL - RANK #36/326
This study aimed to evaluate the efficacy and safety of regorafenib (REGO) in patients with advanced, heavily pretreated melanoma via a single-center, phase II clinical trial. The study recruited 16 patients with advanced melanoma and assessed the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety outcomes. Results showed an overall ORR of 37.5%, with disease control rate (DCR) of 56%; KIT-mutant and BRAF-mutant subpopulations exhibited higher responses and longer median PFS and OS, particularly in KIT-mutant patients where ORR was 78% and DCR was 100%. Grade 3 treatment-related adverse events (TRAEs) were reported in 59% of monotherapy patients and 50% of combination therapy patients, with all events reversible, supporting further investigation of REGO-based regimens in this population.
10.1016/j.esmoop.2026.106941
A first-in-human phase 1 clinical trial evaluating clinical activity and proof-of-mechanism of tobemstomig, a PD1-LAG3 bispecific antibody, in patients with CPI-experienced melanoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This study is a first-in-human, open-label, phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the PD1-LAG3 bispecific antibody, tobemstomig, in patients with advanced and/or metastatic solid tumors. The study included 35 patients in the dose-escalation phase and 69 patients in the expansion phase, across various tumor types. Partial responses were observed in 15% (6/41) of CPI-experienced melanoma patients and proof-of-mechanism was demonstrated by increased CD8+ T cell activity, among other immunological effects. Tobemstomig demonstrated a tolerable safety profile with a recommended dose established at 2100 mg Q2W, supporting further investigation in earlier disease settings.
10.1158/1078-0432.CCR-25-4478